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论文类型：期刊论文

发表时间：2013-08-01

发表刊物：JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

收录刊物：SCIE、Scopus

卷号：31

期号：8

页面范围：841-853

ISSN号：0739-1102

关键字：eIF-4A; Leishmania; Listeria; adjuvant; epitope; normal mode; vibration; molecular dynamics

摘要：Recent homology modeling studies have identified specific residues (epitope) of the Leishmania RNA helicase protein (LmeIF) that stimulates production of IL-12 cytokine. However, question remains concerning how LmeIF's N-terminal moiety initiates adjuvant effects. Extensive molecular modeling combining the normal mode analysis (NMA) and molecular dynamics simulations, in the present study, has demonstrated that the LmeIF structure may exist in two different forms corresponding to the extended and collapsed (closed) states of the entire structure. The computational results showed that the two domains of the LmeIF structure tend to undergo large fluctuations in a concerted fashion and have strong effect on the solvent accessible surface of the epitope situated on the N-terminal structure. The conformational freedom of the C-terminal domains may explain why the entire LmeIF protein is not as active as the N-terminal moiety. Thereafter, a comparative genome analysis with subsequent homology modeling and molecular electrostatic potential (MEP) techniques allowed us to predict a novel and plausible RNA helicase (LI-helicase) from the Listeria source with adjuvant property as observed for the Leishmania eIF-4A protein. The structural folding and MEP maps revealed similar topologies of the epitope of both LmeIF and LI-helicase proteins and striking identity in the local disposition of the charged groups. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at